Cystatin-C is an independent prognostic factor for survival in multiple myeloma and is reduced by bortezomib administration
Open Access
- 1 March 2009
- journal article
- clinical trial
- Published by Ferrata Storti Foundation (Haematologica) in Haematologica
- Vol. 94 (3), 372-379
- https://doi.org/10.3324/haematol.2008.000638
Abstract
Renal impairment is a common complication of multiple myeloma. Cystatin-C is considered an accurate marker of glomerular filtration rate in several renal disorders. Microarray analysis has revealed that cystatin-C is one of the most highly up-regulated genes in multiple myeloma. The aim of this study was to evaluate the serum levels of cystatin-C in myeloma patients, explore possible correlations with clinical data, including survival, and assess the effect of bortezomib on cystatin-C in relapsed multiple myeloma. We measured serum cystatin-C in 157 newly diagnosed, previously untreated myeloma patients, in 28 patients with relapsed disease pre- and post-bortezomib therapy and in 52 healthy controls, using a latex particle-enhanced nephelometric immunoassay. In newly diagnosed patients, cystatin-C was elevated and showed strong correlations with advanced ISS stage, extensive bone disease, high beta(2)-microglobulin, high serum creatinine, and low creatinine clearance. Multivariate analysis revealed that only cystatin-C and lactate dehydrogenase had an independent prognostic impact on patients' survival. The combination of cystatin-C and lactate dehydrogenase revealed three prognostic groups of patients: a high-risk group (both elevated cystatin-C and lactate dehydrogenase) with a median survival of 24 months, an intermediate-risk group (elevated cystatin-C or elevated lactate dehydrogenase) with a median survival of 48 months and a low-risk group (both low cystatin-C and lactate dehydrogenase) in which median survival has not yet been reached (p<0.001). Cystatin-C could also identify a subset of ISS-II patients with worse outcome. Relapsed patients had higher cystatin-C levels even compared to newly diagnosed patients. Treatment with bortezomib produced a significant reduction of cystatin-C, mainly in responders. Serum cystatin-C is not only a sensitive marker of renal impairment but also reflects tumor burden and is of prognostic value in myeloma. Its reduction after treatment with bortezomib reflects bortezomib's anti-myeloma activity and possibly bortezomib's direct effect on renal function.Keywords
This publication has 40 references indexed in Scilit:
- Estimating GFR Using Serum Cystatin C Alone and in Combination With Serum Creatinine: A Pooled Analysis of 3,418 Individuals With CKDAmerican Journal of Kidney Diseases, 2008
- Serum cystatin C in the aged: relationships with health statusAmerican Journal of Kidney Diseases, 2003
- Serum Cystatin C and β2-Microglobulin as Markers of Glomerular Filtration RateRenal Failure, 2003
- Comparison of gene expression profiling between malignant and normal plasma cells with oligonucleotide arraysOncogene, 2002
- Serum cystatin C is superior to serum creatinine as a marker of kidney function: A meta-analysisAmerican Journal of Kidney Diseases, 2002
- Effect of corticosteroid therapy on serum cystatin C and beta2-microglobulin concentrations.2002
- Effects of Glucocorticoid Immunosuppression on Serum Cystatin C Concentrations in Renal Transplant PatientsClinical Chemistry, 2001
- Serum cystatin C in patients with myelomaClinica Chimica Acta; International Journal of Clinical Chemistry, 2001
- Screening for renal disease using serum creatinine: who are we missing?Nephrology Dialysis Transplantation, 2001
- Renal manifestations of plasma cell dyscrasias: An appraisal from the patients' bedside to the research laboratoryAnnals of Diagnostic Pathology, 2000